p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.

p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding.
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DOI:
10.1083/jcb.201009067
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发表时间:
2011-01-10
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Mizushima N
Mizushima N
中科院分区:
其他
文献类型:
--
作者:
Itakura E;Mizushima N

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p62在早期自噬体形成时被募集到内质网,独立于大多数Atg蛋白。自噬是胞内降解过程,胞质内容物在溶酶体中降解。除了非选择性地吞噬细胞质物质外,自噬体膜还可以选择性地识别特定的蛋白质和细胞器。一般认为,主要的选择性底物(或货物受体)p62通过与LC3的相互作用被招募到自噬体膜上。在本研究中,我们分析了p62及其相关蛋白NBR1的负载,发现它们定位于内质网(ER)相关的自噬体形成位点,而不依赖于LC3定位于膜。p62与上游自噬因子如ULK1和VMP1共定位,即使自噬体的形成被wortmannin或FIP200敲除阻断。p62的自寡聚化是其定位到自噬体形成位点的必要条件。这些结果表明p62定位于内质网上自噬体形成的位置,自噬体在这里成核。这一过程类似于酵母细胞质到液泡的靶向途径。
p62 is recruited to the ER at an early-stage autophagosome formation independently of most Atg proteins. Autophagy is an intracellular degradation process by which cytoplasmic contents are degraded in the lysosome. In addition to nonselective engulfment of cytoplasmic materials, the autophagosomal membrane can selectively recognize specific proteins and organelles. It is generally believed that the major selective substrate (or cargo receptor) p62 is recruited to the autophagosomal membrane through interaction with LC3. In this study, we analyzed loading of p62 and its related protein NBR1 and found that they localize to the endoplasmic reticulum (ER)–associated autophagosome formation site independently of LC3 localization to membranes. p62 colocalizes with upstream autophagy factors such as ULK1 and VMP1 even when autophagosome formation is blocked by wortmannin or FIP200 knockout. Self-oligomerization of p62 is essential for its localization to the autophagosome formation site. These results suggest that p62 localizes to the autophagosome formation site on the ER, where autophagosomes are nucleated. This process is similar to the yeast cytoplasm to vacuole targeting pathway.
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